Left Ventricular Systolic Function in Long-Term Survivors of Allogeneic Hematopoietic Stem Cell Transplantation

Abstract Clonal hematopoiesis (CH) is associated with age and an increased risk of myeloid malignancies, cardiovascular risk, and all-cause mortality. We tested for CH in a setting where hematopoietic stem cells (HSCs) of the same individual are exposed to different degrees of proliferative stress and environments, ie, in long-term survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their respective related donors (n = 42 donor-recipient pairs). With a median follow-up time since allo-HSCT of 16 years (range, 10-32 years), we found a total of 35 mutations in 23 out of 84 (27.4%) study participants. Ten out of 42 donors (23.8%) and 13 out of 42 recipients (31%) had CH. CH was associated with older donor and recipient age. We identified 5 cases of donor-engrafted CH, with 1 case progressing into myelodysplastic syndrome in both donor and recipient. Four out of 5 cases showed increased clone size in recipients compared with donors. We further characterized the hematopoietic system in individuals with CH as follows: (1) CH was consistently present in myeloid cells but varied in penetrance in B and T cells; (2) colony-forming units (CFUs) revealed clonal evolution or multiple independent clones in individuals with multiple CH mutations; and (3) telomere shortening determined in granulocytes suggested ∼20 years of added proliferative history of HSCs in recipients compared with their donors, with telomere length in CH vs non-CH CFUs showing varying patterns. This study provides insight into the long-term behavior of the same human HSCs and respective CH development under different proliferative conditions.

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Cardiovascular Complications in Long-Term Survivors After Allogeneic Hematopoietic Stem Cell Transplantation

Seminars in Hematology ◽

10.1053/j.seminhematol.2011.10.001 ◽

2012 ◽

Vol 49 (1) ◽

pp. 25-34 ◽

Cited By ~ 21

Author(s):

Alicia Rovó ◽

André Tichelli

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Cardiovascular Complications ◽

Hematopoietic Stem ◽

Long Term Survivors

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Hematopoietic Stem Cell Transplantation and Secondary Primary Malignancies in Taiwan

Blood ◽

10.1182/blood.v120.21.4219.4219 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4219-4219 ◽

Cited By ~ 1

Author(s):

Chia-Jen Liu ◽

Kuo-Wei Chen ◽

Yu-Wen Hu ◽

Ying-Chung Hong ◽

Yu-Chung Huang ◽

...

Keyword(s):

Stem Cell ◽

Soft Tissue ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Hematological Malignancies ◽

Soft Tissue Sarcomas ◽

Cancer Development ◽

Hematopoietic Stem ◽

Long Term Survivors

Abstract Abstract 4219 Objectives Hematopoietic stem cell transplantation (HSCT) is a curative strategy for many hematological disorders. The improvement of HSCT may lead to longer overall survival of patients with catastrophic illness and the risk of secondary cancer development become an emerging issue in long-term survivors. Patients and Methods We conducted a nationwide population-based study of 1,881 patients with hematologic diseases undergoing HSCT between January, 1997 and January, 2007 using Taiwan's National Health Insurance Research database. Performing HSCT to treat non-hematological diseases were excluded. All patients were followed until solid cancer development, death, or the end of 2010. We did not put hematological malignancies as endpoint because solid tumors and hematological malignancies might have different carcinogensis mechanism. We used standardized incidence ratios (SIRs) to compare patterns of cancer incidence in patients with those of the general population. Multivariate analysis was undertaken using Cox proportional-hazards regression using a forward selection, likelihood ratio model to identify independent predictors of cancer development among patients after HSCT. Results We observed a total of 8,753.87 person-years in this study. Patients received HSCT had a significant increased risk of developing any kind of cancer (SIR 1.77, 95% confidence interval [CI] 1.15 – 2.62; p = 0.011). Specifically, patients after HSCT had increased cancer incidence of head and neck cancer (SIR 3.96, 95% CI 1.90 – 7.29; p < 0.001) and bone and soft tissue sarcomas (SIR 10.08, 95% CI 1.22 – 36.42; p = 0.035). In subgroup analyses, cancers were more likely to develop in patients aged 0 – 19 years (SIR 22.31, 95% CI 4.60 – 65.20; p < 0.001), and those who survived more than 5 years after HSCT (SIR 3.30, 95% CI 1.96 – 5.22; p < 0.001). Conclusion Our study demonstrates an increased incidence of cancer development in patients after HSCT, especially malignancies of head and neck and also bone and soft tissue sarcomas. Patients aged 0 – 19 years and those survived more than 5 years after HSCT have a higher incidence of developing cancer comparing to normal population. HSCT long-term survivors should therefore be monitored more carefully for cancer development and targeted with preventive intervention strategies. Disclosures: No relevant conflicts of interest to declare.

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